Aminophylline reduces hypoxic ventilatory depression in newborn piglets and can enhance the release of catecholamines (CATs), which in turn may stimulate ventilation. To determine if the effect of aminophylline on ventilation was due to the release of CATs, we measured plasma CATs and ventilation in two groups of spontaneously breathing newborn piglets less than 4 days old, treated with either aminophylline (n = 7) or normal saline solution (n = 6) during both normoxia and hypoxia. The piglets were anesthetized with ketamine and xylazine and intubated, and the femoral artery was catheterized. Epinephrine and norepinephrine were measured before and 30 minutes after treatment with aminophylline (15 mg/kg) or normal saline. The animals were exposed to 10% oxygen and the CATs again measured after 5 minutes of hypoxia. Respiratory rate, expiratory flow integrated to minute ventilation (VE), heart rate, and blood pressure were continuously recorded. CATs were assayed by high-pressure liquid chromatography with electrochemical detection. Treatment with aminophylline during normoxia was associated with an increase in tidal volume. During hypoxia, treatment with aminophylline prevented a fall in VE and respiratory rate seen in the normal saline group. Epinephrine and norepinephrine increased during hypoxia, but there was no difference between the groups at 5 minutes. In our model the increase in CATs observed during hypoxia was not enhanced by aminophylline. This is consistent with the hypothesis that some mechanism other than catecholamine release is responsible for the effect of aminophylline in reducing neonatal hypoxic respiratory depression.